It is known to those skilled in the art that progestogenic steroids, either singly or in combination, may be used to control the fertility of warm blooded animals. Various products and three primary regimens are presently in use and in particular the following:
Combination regimens containing an estrogen and a progestogen which are generally administered from day five of a menstrual cycle for 20 or 21 days;
Sequential/serial regimens in which an estrogen is administered generally from day five of the cycle followed sequentially by an estrogen-progestogen combination, various regimens of which have been proposed; and continuous progestogen regimen (or mini-pill) in which a progestogen is administered daily.
Combination regimen and sequential/serial regimen inhibit ovulation with great efficiency. Continuous progestogen regimen utilizes a dose of steroidal progestogen so small that it does not induce ovulation inhibition in the majority of users who continue to ovulate and to cycle essentially as they would without progestogen. However, as is well known to those skilled in the art, use of this regimen is accompanied by a sufficiently high incidence of uterine spotting and extended bleeding to markedly reduce the utility and attractiveness of the method for contraception and as an instrument for population control. Various proposals have been made for reducing the incidence of spotting and extended bleeding, for example, the addition of estrogen to the progestogen for the last few days of each cycle.
Although estrogens have proven to provide an effective means of contraception it is known that certain undesirable side effects may result from their use. Ethinyl estradiol and mestranol, which represent estrogenic components in current oral contraceptives, are known to be involved in certain serious side effects associated with oral contraceptives including depression (Nature 243, 58 (1973)), hypertension (Am. J. Obstet. Gynecol. 112, 912 (1972)), carbohydrate and lipid abnormalities (Lancet 1969, October 11, 783), interference with blood clotting mechanisms resulting in thrombosis and stroke (Ann. Intern Med. 72, 111 (1970)), and jaundice (Am. J. Obstet. Gynecol. 119, 165 (1974)). Consequently, there is a need for an improved method of contraception.
The present invention provides a novel method of contraception which avoids many of the undesirable side effects which may occur with the use of estrogens as will become more apparent hereinafter.
Some of the compounds employed in the instant invention, for example, 19-hydroxyandrost-4-ene-3,17-dione and the 19-oxo derivative thereof have been involved in numerous in vitro studies wherein the role in the metabolism of androgen has been investigated. Additionally, 19-hydroxy- androst-4-ene-3,17-dione is reported to have been administered to two healthy male subjects each 21 years of age (J. Clin. Endocrinol. Metab. 28, 1401 (1968)). Also, 3-oxo-17.beta.-hydroxyandrost-4-en-19-al has been reported in U.S. Pat. No. 3,235,573issued Feb. 15, 1966, and U.S. Pat. No. 3,449,381 issued June 10. 1969 wherein the utilities disclosed are anabolic-androgenic activity, inhibition of pituitary gonadotrophins and adrenocorticotrophin, antiestrogenic, blood, liver and adrenal cholesterol lowering properties, control of fertility and psychotic conditions, and appetite stimulants. To applicant's knowledge the use of the compounds employed in the present invention as contraceptive agents by the inhibition of ovulation has not been taught or suggested heretofore.